Studies of internal iron kinetics include an evaluation of differences in clearance of iron from mono- and diferric transferrin in normal subjects and in patients with various red cell disorders. In animals the importance of marrow iron flow will be evaluated. Regulatory mechanisms affecting iron donation to transferrin are also being studied. Studies of iron overload include observations on patients with idiopathic hemochromatosis, on their relatives, and on individuals in the population at large who show excessive stores. The action of iron chelates is also being evaluated. Tissue effects of iron deficiency are being studied. A muscle abnormality resulting in lactic acidosis with exertion has been described. Evidence has also been obtained that maintenance of body temperature is impaired in iron deficient animals and that this is due to a deficient tissue conversion of T4 to T3. Other studies relate to the effects of hypertransfusion on erythropoiesis and on bone metabolism in the experimental animal and in thalassemia, and the effects of tumor on marrow proliferation.